Retention of osteocytic micromorphology by sclerostin antibody in a concurrent ovariectomy and functional disuse model. Issue 1 (15th January 2019)

• Record Type: Journal Article
• Authors: Zhang, Dongye; Miranda, Mariana; Li, Xiaofei; Han, Jiangmeng; Sun, Yueli; Rojas, Nancy; He, Shan; Hu, Minyi; Lin, Liangjun; Li, Xiaodong; Ke, Hua Zhu; Qin, Yi‐Xian
• Editors: Sun, Hui B.
• Is Part Of: Annals of the New York Academy of Sciences. Volume 1442:Issue 1(2019)
• Page Start: 91
• Page End: 103
• Publication Date: 2019-01-15
• Subjects: sclerostin antibody -- osteocyte -- severe osteoporosis -- scanning electron microscopy -- mechanical unloading -- estrogen deficiency; Medical sciences -- Periodicals; Medicine -- Periodicals; Science -- Periodicals; 610
• DOI: 10.1111/nyas.13991
• Languages: English
• ISSNs: 0077-8923

Abstract

Abstract: Prolonged mechanical unloading in bedridden patients and concurrent hormonal dysregulation represents the cause of one of the severest forms of osteoporosis, a condition for which there are very few efficacious interventions available to date. Sclerostin, a Wnt antagonist, acts as a negative regulator of bone formation. Sclerostin antibody (Scl‐Ab)–mediated blockade of sclerostin can dramatically enhance bone formation and reduce bone resorption. This study was designed to investigate the therapeutic effect of the Scl‐Ab on severe bone loss induced by concurrent mechanical unloading and estrogen deficiency in a hindlimb‐suspended and ovariectomized rat model, and to study the cellular mechanisms underlying severe osteoporosis and Scl‐Ab action. Unloading and ovariectomy resulted in severe loss of trabecular and cortical bone mass and strength; Scl‐Ab can significantly counteract the deterioration of bone in unloaded and/or ovariectomized rats, with noticeably increased cortical bone formation. Scanning electron microscopy analysis revealed that unloading and ovariectomy lead to multiple morphological and structural abnormalities of osteocytes in cortical bone and the abnormalities were abolished by Scl‐Ab administration. This study extends our previous conclusion that Scl‐Ab represents a promising therapeutic approach for severe bone loss that occurs after being exposed to estrogen deficiency and prolonged mechanical unloading. Abstract : This paper investigates the therapeutic effect of the sclerostin antibody on severe bone loss induced by concurrent mechanical unloading and estrogen deficiency in a hindlimb‐suspended and ovariectomized rat model, and examines the cellular mechanisms underlying severe osteoporosis and sclerostin antibody action.